Publication
Title
Opposing effects of HLA class I molecules in tuning autoreactive T cells in multiple sclerosis
Author
Abstract
The major known genetic risk factors in multiple sclerosis reside in the major histocompatibility complex (MHC) region. Although there is strong evidence implicating MHC class II alleles and CD4+ T cells in multiple sclerosis pathogenesis, possible contributions from MHC class I genes and CD8+ T cells are controversial. We have generated humanized mice expressing the multiple sclerosisassociated MHC class I alleles HLA-A*0301 (encoding human leukocyte antigen-A3 (HLA-A3)) and HLA-A*0201 (encoding HLA-A2) and a myelin-specific autoreactive T cell receptor (TCR) derived from a CD8+ T cell clone from an individual with multiple sclerosis to study mechanisms of disease susceptibility. We demonstrate roles for HLA-A3restricted CD8+ T cells in induction of multiple sclerosislike disease and for CD4+ T cells in its progression, and we also define a possible mechanism for HLA-A*0201mediated protection. To our knowledge, these data provide the first direct evidence incriminating MHC class I genes and CD8+ T cells in the pathogenesis of human multiple sclerosis and reveal a network of MHC interactions that shape the risk of multiple sclerosis.
Language
English
Source (journal)
Nature medicine. - London, 1995, currens
Publication
London : 2008
ISSN
1078-8956 [print]
1546-170X [online]
Volume/pages
14:11(2008), p. 1227-1235
ISI
000260751200042
Full text (Publisher's DOI)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
External links
Web of Science
Record
Identification
Creation 21.09.2012
Last edited 21.11.2017